1paq
From Proteopedia
CRYSTAL STRUCTURE OF THE CATALYTIC FRAGMENT OF EUKARYOTIC INITIATION FACTOR 2B EPSILON
Structural highlights
Function[EI2BE_YEAST] Acts as a catalytic component of the translation initiation factor 2B (eIF2-B or GCD complex), which catalyzes the exchange of eukaryotic initiation factor 2 (eIF-2)-bound GDP for GTP and is regulated by phosphorylated eIF-2. It activates the synthesis of GCN4 in yeast under amino acid starvation conditions by suppressing the inhibitory effects of multiple AUG codons present in the leader of GCN4 mRNA. It may promote either repression or activation of GCN4 expression depending on amino acid availability. GCD6 and GCD7 repress GCN4 expression at the translational level by ensuring that ribosomes which have translated UORF1 will reinitiate at UORF2, -3, or -4 and thus fail to reach the GCN4 start site.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedEukaryotic initiation factor (eIF) 2B catalyzes the nucleotide activation of eIF2 to its active GTP-bound state. The exchange activity has been mapped to the C terminus of the eIF2Bepsilon subunit. We have determined the crystal structure of residues 544-704 from yeast eIF2Bepsilon at 2.3-A resolution, and this fragment is an all-helical protein built around the conserved aromatic acidic (AA) boxes also found in eIF4G and eIF5. The eight helices are organized in a manner similar to HEAT repeats. The molecule is highly asymmetric with respect to surface charge and conservation. One area in the N terminus is proposed to be directly involved in catalysis. In agreement with this hypothesis, mutation of glutamate 569 is shown to be lethal. An acidic belt and a second area in the C terminus containing residues from the AA boxes are important for binding to eIF2. Two mutations causing the fatal human genetic disease leukoencephalopathy with vanishing white matter are buried and appear to disrupt the structural integrity of the catalytic domain rather than interfering directly with catalysis or binding of eIF2. Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue.,Boesen T, Mohammad SS, Pavitt GD, Andersen GR J Biol Chem. 2004 Mar 12;279(11):10584-92. Epub 2003 Dec 17. PMID:14681227[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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